Field of the Invention
The present embodiments relate to machines and methods of preparation of biological samples based on a signal generated by the sample. More specifically, the present embodiments relate to a device that uses image analysis for process control of the preparation of the sample.
Description of the Related Art
Correlative Light and Electron Microscopy (CLEM) is a well-known method that involves a set of procedures that correlates the information found in light microscopy of a sample with information from electron microscopy of that sample. However, many different procedures need to take place to prepare a sample that has been analyzed under light microscopy for use in electron microscopy. Light microscopy works for dynamic living cells, whereas electron microscopy relies upon fixed and processed samples. For example, biological specimens such as cells or tissue need to be properly prepared in various ways to stabilize them, reduce their thickness (ultrathin sectioning) and increase their electron optical contrast (staining) in order to be properly analyzed with electron microscopy.
In many cases CLEM is used to study biological events occurring within particular cells or tissues. For example, the kinetics of fluorescent proteins that are introduced into a cell can be determined and then the cell fixed for electron microscopy by taking the sample and performing a series of experiments to fix and process that sample. This allows the biological samples to be viewed them under an electron microscope. However, there is currently no comprehensive and consistent way to process samples observed through a light microscope so that they are automatically, reproducibly and conveniently processed for electron microscopy.